We have measured regional cerebral blood flow (rCBF) with oxygen-15 and positron emission tomography in normal subjects during performance of a battery of frontal lobe tasks putatively involving working memory as well as during performance of matched sensorimotor control tasks for each frontal lobe test. The results indicate that tasks involving working memory activate a cortical network including dorsolateral prefrontal cortex, superior parietal cortex (particularly the inferior parietal lobule and area 7), and inferior temporal cortex in humans. During more complex tasks hippocampus is also activated. We have recently shown that the acquisition, but not the retrieval of spatial data involves the frontal cortex, particularly on the right. We have also shown that the degree to which CBF differs between men and women depends on their cognitive state during the scan. Studies of normal monozygotic twins aimed at determining the degree of heritability of cognitively-related regional brain function had suggested that while there are more similarities between twins than between age and sex-matched unrelated individuals, the degree of genetic influence may not be large. A new comparison with normal dizygotic twins has allowed the relative contributions of heritability and common environmental effects on cognitively-related rCBF to be calculated. The results to date indicate that the contributions of both environmental and hereditary factors to rCBF pattern are greater than to rCBF level.